Synonym
Flumatinib mesylate; HHGV678; HHGV 678 ; HHGV-678; HH-GV-678; Flumatinib;
IUPAC/Chemical Name
N-(6-methyl-5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)pyridin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide mesylate
InChi Key
ZSASDYCFROUKTJ-UHFFFAOYSA-N
InChi Code
InChI=1S/C29H29F3N8O.CH4O3S/c1-19-26(38-28-34-9-7-25(37-28)21-4-3-8-33-16-21)15-23(17-35-19)36-27(41)20-5-6-22(24(14-20)29(30,31)32)18-40-12-10-39(2)11-13-40;1-5(2,3)4/h3-9,14-17H,10-13,18H2,1-2H3,(H,36,41)(H,34,37,38);1H3,(H,2,3,4)
SMILES Code
O=C(NC1=CC(NC2=NC=CC(C3=CC=CN=C3)=N2)=C(C)N=C1)C4=CC=C(CN5CCN(C)CC5)C(C(F)(F)F)=C4.OS(=O)(C)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Flumatinib mesylate (HHGV678 mesylate) is an orally available, selective inhibitor of Bcr-Abl. Flumatinib mesylate inhibits c-Abl, PDGFRβ and c-Kit with IC50s of 1.2 nM, 307.6 nM and 665.5 nM, respectively.
In vitro activity:
In 32D-V559D + Y823D cells, the phosphorylation levels of KIT, ERK1/2, and STAT3 were strongly inhibited by flumatinib, but not imatinib or sunitinib (Fig. 2). Similar findings were observed in 32D-V559D + N822K and 32D-V559D + A829P cells (Fig. S1). These results collectively show that flumatinib is capable of overcoming the imatinib and sunitinib resistance conferred by certain secondary activation loop mutations in vitro.
Reference: Cancer Sci. 2014 Jan; 105(1): 117–125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317885/
In vivo activity:
In contrast, treatments with imatinib (150 mg/kg, b.i.d.) and flumatinib (75 mg/kg, q.d. and b.i.d.) extended the median survival to 23.5 (P = 0.23), 25.5 (P = 0.061), and 25.5 (P < 0.05) days, relative to the vehicle-treated group, respectively (Fig. 3). In addition, the survival of mice treated with flumatinib (75 mg/kg, b.i.d.) was significantly improved compared with mice treated with imatinib (150 mg/kg, q.d.; P < 0.01) or sunitinib (50 mg/kg, q.d.; P < 0.01).
Reference: Cancer Sci. 2014 Jan; 105(1): 117–125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317885/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
75.91 |
| Water |
50.0 |
75.91 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
658.70
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PMID: 24205792; PMCID: PMC4317885.
In vitro protocol:
1. Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PMID: 24205792; PMCID: PMC4317885.
In vivo protocol:
1. Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PMID: 24205792; PMCID: PMC4317885.
1: Chang MX, Ma YP. [Effect of flumatinib mesylate on C-MYC, HIF-1α and VEGF in U226 line]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Dec;21(6):1496-500. doi: 10.7534/j.issn.1009-2137.2013.06.024. Chinese. PubMed PMID: 24370036.
2: Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PubMed PMID: 24205792; PubMed Central PMCID: PMC4317885.
3: Yang Y, Liu K, Zhong D, Chen X. Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 May 1;895-896:25-30. doi: 10.1016/j.jchromb.2012.03.008. Epub 2012 Mar 15. PubMed PMID: 22472641.
4: Luo H, Quan H, Xie C, Xu Y, Fu L, Lou L. HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistance. Leukemia. 2010 Oct;24(10):1807-9. doi: 10.1038/leu.2010.169. Epub 2010 Aug 12. PubMed PMID: 20703259.
5: Gong A, Chen X, Deng P, Zhong D. Metabolism of flumatinib, a novel antineoplastic tyrosine kinase inhibitor, in chronic myelogenous leukemia patients. Drug Metab Dispos. 2010 Aug;38(8):1328-40. doi: 10.1124/dmd.110.032326. Epub 2010 May 17. PubMed PMID: 20478851.
6: Qiu L, Wang XD, Yu BH, Lu RZ, Ge F, Wang XL, Chen LJ, Han BH, Zhan ZM, Zhang BL, Ma J. [Effect of a novel tyrosine kinase inhibitor HHGV678 on growth inhibition of Bcr-Abl wild type and IM-resistant cell lines in vitro]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Oct;16(5):1039-43. Chinese. PubMed PMID: 18928591.
